Control of enzymatic function is provided in certain cases through synthesis of a zymogen or proenzyme that contains extra stretches of polypeptide chain. The extra material serves to limit activity by inducing an inactive conformation or by blocking the active site. Understanding this process on a molecular level will provide valuable insights into the modulation of protein function by peptide binding. Uncontrolled secretion and/or activation of pepsin may play a role in the production of peptic ulcers. Modulation of the activity of pepsin might play an important role in the management of ulcerative diseases. Pepsinogen is activated to pepsin by the release of 44 amino acid residues from the amino terminus. Several studies have isolated peptides from the activation mixture that act as inhibitors by mimicking the action of the amino terminal in the zymogen. We propose to purify these peptides from activation of the zymogen, definitively establish their structure, and study their interaction with the active enzyme species by numerous kinetic and spectral techniques. Following this we will synthesize these peptides of known sequence by the solid-phase technique, purifying the products by forming semisynthetic complexes or by affinity chromatography. We also propose to prepare synthetic analogues of the native peptide sequence to probe the critical structural features in this molecular association.